For psoriasis, targeting skin protein may help control inflammation
When tested in mice, psoriasis became more severe when more interferon
kappa was present.

Date:
August 12, 2021
Source:
Michigan Medicine - University of Michigan
Summary:
Results from a new study reveal that targeting interferon kappa,
a protein made by skin cells, may reduce the severity of psoriasis.

Researchers say the findings will bring physicians one step closer
to optimizing treatments for patients with the autoimmune disease.



FULL STORY ========================================================================== Results from a Michigan Medicine study reveal that targeting a protein
found in the skin may reduce the severity of psoriasis.


========================================================================== Interferons play a major role in activating the body's response to
viral threats, but they have also been detected in the lesions of many psoriasis patients at abnormal levels. Psoriasis is an autoimmune disease
that causes overproduction of skin cells and impacts nearly 30 million
people in the world.

Using a model that mimics psoriasis in mice, researchers found that
changing the levels of interferon kappa, a protein made by skin cells,
altered the severity of inflammation and production of cell signaling molecules, called cytokines, that induce inflammation characteristic of psoriasis. Investigators found more psoriasis-like inflammation when
more interferon kappa was present, while decreasing interferon kappa
levels reduced disease.

The findings, published in the Journal of Investigative
Dermatology,suggest using therapies to modulate interferon states may
limit inflammation in psoriasis patients.

"We've known that psoriatic inflammation is marked by interferon-related
gene expression, but how interferons alter the severity of the disease
has not been clear," said J. Michelle Kahlenberg, M.D., Ph.D., associate professor of rheumatology at Michigan Medicine and senior author of
the paper.

"Understanding how interferon kappa may modulate psoriasis brings us one
step closer to optimizing our treatments." The research team induced
psoriasis in mouse models, splitting them into groups with interferon
kappa at low, normal or elevated levels. The overexpressed protein alone
didn't induce the disease, but it primed the skin for the inflammatory
response that followed.

"This work shows how the context of the skin environment can shape
inflammatory responses." said Mehrnaz Gharaee-Kermani, DVM, M.P.H., Ph.D.,
lead author of the study and a senior research lab specialist at Michigan Medicine. "It will be exciting to see how this can be applied in clinic."
The research team is conducting further studies to understand the role of interferon kappa in psoriasis patients through their Taubman Institute- sponsored study at Michigan Medicine and in partnership with Johann E.

Gudhonsson, M.D., Ph.D., receiving funding through the National Psoriasis Foundation. Several treatments are used against the disease, but there
is no cure.

A few current psoriasis drugs inhibit interferons, but many that are more specific are still in the trial phase. Coupled with the study's findings, personalized medicine will be paramount as physicians attempt to treat
this disease, Kahlenberg said.

"Until now, treatments have been tested by studying a drug in
hundreds of patients, lumping the average of them all together and
targeting the average of those patients," Kahlenberg said. "As
any patient who has been on these medications will tell you,
this trial-and-error approach wastes patient time and money
trying to get control of the disease. Understanding a patient's
background level of interferon might help us target things within
that person to make their disease better faster and stay in remission." ========================================================================== Story Source: Materials provided by
Michigan_Medicine_-_University_of_Michigan. Original written by Noah
Fromson. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Mehrnaz Gharaee-Kermani, Shannon N. Estadt, Lam C. Tsoi, Sonya
J. Wolf,
Jianhua Liu, Xianying Xing, Jonathon Theros, Tammi J. Reed, Lori
Lowe, Dennis Gruszka, Nicole L. Ward, Johann E. Gudjonsson,
J. Michelle Kahlenberg. Interferon Kappa Is a Rheostat for
Development of Psoriasiform Inflammation. Journal of Investigative
Dermatology, 2021; DOI: 10.1016/j.jid.2021.05.029 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210812092737.htm

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